Poly (ADP-Ribosylation) and DNA Topoisomerase I in Different Cell Lines

Ferro, Ari M.; Thompson, Larry H.; Olivera, Baldomero M.

doi:10.1007/978-1-4684-8730-5_45

Cited by 37 publications

(39 citation statements)

References 25 publications

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“…their activity (Ferro and Olivera, 1984;Darby et al, 1985). Consistent with these observations Mattern et al (1987) demonstrated potentiation of camptothecin and teniposide cytotoxicity by the PARP inhibitor, 3-aminobenzamide (3AB), in L1210 cells.…”

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confidence: 68%

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

et al. 2001

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The potent novel poly(ADP-ribose) polymerase (PARP) inhibitor, NU1025, enhances the cytotoxicity of DNA-methylating agents and ionizing radiation by inhibiting DNA repair. We report here an investigation of the role of PARP in the cellular responses to inhibitors of topoisomerase I and II using NU1025. The cytotoxicity of the topoisomerase I inhibitor, camptothecin, was increased 2.6-fold in L1210 cells by co-incubation with NU1025. Camptothecin-induced DNA strand breaks were also increased 2.5-fold by NU1025 and exposure to camptothecin-activated PARP. In contrast, NU1025 did not increase the DNA strand breakage or cytotoxicity caused by the topoisomerase II inhibitor etoposide. Exposure to etoposide did not activate PARP even at concentrations that caused significant levels of apoptosis. Taken together, these data suggest that potentiation of camptothecin cytotoxicity by NU1025 is a direct result of increased DNA strand breakage, and that activation of PARP by camptothecin-induced DNA damage contributes to its repair and consequently cell survival. However, in L1210 cells at least, it would appear that PARP is not involved in the cellular response to etoposide-mediated DNA damage. On the basis of these data, PARP inhibitors may be potentially useful in combination with topoisomerase I inhibitor anticancer chemotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.com

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confidence: 68%

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

et al. 2001

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“…It has been reported that inhibitors of PARP-1 could potentiate the cytotoxicity of camptothecin and topotecan, another topoisomerase I inhibitor, suggesting that PARP-1 is somehow involved with topoisomerase I in modulating camptothecin action (24). It was also reported that PARP-1 poly(ADPribosyl)ated topoisomerase I, in the presence of NAD, results in the inhibition of topoisomerase I relaxation activity (25,26). The underlying mechanism responsible for inhibiting activity was suggested to be due to the large increase in net negative charge upon poly(ADP-ribosyl)ation of topoisomerase I, which eventually causes repulsion between topoisomerase I and DNA.…”

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confidence: 99%

Poly(ADP-Ribose) Polymerase-1 Could Facilitate the Religation of Topoisomerase I-linked DNA Inhibited by Camptothecin

Park

Cheng

2005

Cancer Research

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Poly(ADP-ribose) polymerase-1 (PARP-1) is known to have an important role in camptothecin sensitivity and interacts with topoisomerase I. In the present study, the impact of PARP-1 on the topoisomerase I-DNA complex stabilized by camptothecin was assessed. It was shown that NH 2 terminustruncated topoisomerase I (amino acids 201-765) showed at least 4-fold less sensitivity to camptothecin than full-length topoisomerase I in the oligonucleotide religation assay. PARP-1 could prevent the action of camptothecin on the religation activity of full-length topoisomerase I, which is linked to DNA in a stoichiometrical manner. However, the religation activity of NH 2 terminus-truncated topoisomerase I, which is linked to DNA, could not be enhanced by PARP-1 in the presence of camptothecin. Both full-length and NH 2 terminus-truncated topoisomerase I interact with PARP-1. This data suggests that PARP-1 destabilizes the topoisomerase I-camptothecin-DNA complex with the participation of the NH 2 -terminal domain of topoisomerase I. Poly(ADP-ribosyl)ation of topoisomerase I by PARP-1 in the presence its substrate, NAD, could also promote the religation activity of full-length topoisomerase I as well as NH 2 terminus-truncated topoisomerase I. PARP-1 inhibitors (3-aminobenzamide, PJ34) could inhibit this process. Therefore, PARP-1 could facilitate the religation activity of topoisomerase I by itself through topoisomerase I-PARP-1 interaction (PARP-1 action) or by the formation of poly(ADP-ribosyl)ation of topoisomerase I (PARP-1/NAD action). This study also implies that PARP-1 and PARP-1/ NAD actions need to be highly regulated by cellular factors for camptothecin to exert its cytotoxicity inside the cells. We propose ATP to be one of the important regulatory factors. (Cancer Res 2005; 65(9): 3894-902)

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“…An additional function of poly(ADP-ribose) synthesis may be to modulate directly the activity or function of covalently modified acceptor proteins (enzymes, transcription factors). For example, poly (ADP-ribosylation) of DNA polymerases, ligase and topoisomerase I causes inhibition of these enzymes in vitro (Ferro et al, 1983;Yoshihara et al, 1985). However, little work has been carried out to establish whether these proteins can act as acceptors in intact cells.…”

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confidence: 99%

Potentiation of temozolomide-induced cytotoxicity: a comparative study of the biological effects of poly(ADP-ribose) polymerase inhibitors

Boulton¹,

Pemberton²,

Porteous³

et al. 1995

Br J Cancer

121

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Summary Four poly(ADP-ribose) polymerase (PADPRP) inhibitors [3-aminobenzamide, benzamide, 3,4-dihydro-5-methoxyisoquinolin-1(2H)-one (PD 128763) and 8-hydroxy-2-methylquinazolin-4(3H)-one (NU1025)] were compared with respect to their effects on a number of biological end points. The following parameters were assessed: their ability to inhibit the enzyme in permeabilised L1210 cells; their ability to potentiate the cytotoxicity of temozolomide (including the cytotoxicity of the compounds per se); their ability to increase net levels of temozolomide-induced DNA strand breaks and inhibit temozolomide-induced NAD depletion. PD 128763 and NU1025 were equipotent as PADPRP inhibitors, and 40-and 50-fold more potent than benzamide and 3-aminobenzamide respectively. All the compounds acted in a concentration-dependent manner to potentiate the cytotoxicity and increase DNA strand break levels in cells treated with temozolomide. There was an excellent correlation between the potency of the compounds as PADPRP inhibitors and their effects on cell survival and DNA repair. Temozolomide treatment caused a decrease in cellular NAD levels, and this was abolished by the PADPRP inhibitors. In conclusion, the new generation of PADPRP inhibitors are at least 50-fold more effective than 3-aminobenzamide as chemopotentiators, and can be used at micromolar rather than millimolar concentrations in intact cells.

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Poly (ADP-Ribosylation) and DNA Topoisomerase I in Different Cell Lines

Cited by 37 publications

References 25 publications

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

Poly(ADP-Ribose) Polymerase-1 Could Facilitate the Religation of Topoisomerase I-linked DNA Inhibited by Camptothecin

Potentiation of temozolomide-induced cytotoxicity: a comparative study of the biological effects of poly(ADP-ribose) polymerase inhibitors

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